Vitamin B6: A Molecule for Human Health?

Article (PDF Available)inMolecules 15(1):442-59 · January 2010with25 Reads
DOI: 10.3390/molecules15010442 · Source: PubMed
Vitamin B6 is an intriguing molecule that is involved in a wide range of metabolic, physiological and developmental processes. Based on its water solubility and high reactivity when phosphorylated, it is a suitable co-factor for many biochemical processes. Furthermore the vitamin is a potent antioxidant, rivaling carotenoids or tocopherols in its ability to quench reactive oxygen species. It is therefore not surprising that the vitamin is essential and unquestionably important for the cellular metabolism and well-being of all living organisms. The review briefly summarizes the biosynthetic pathways of vitamin B6 in pro- and eukaryotes and its diverse roles in enzymatic reactions. Finally, because in recent years the vitamin has often been considered beneficial for human health, the review will also sum up and critically reflect on current knowledge how human health can profit from vitamin B6.

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    • "(l) Effect of 4DP (5 and 50 μmol/l) administration on expression of adipogenesis transcriptional markers, such as ADIPOQ, PPARG, GLUT4, PLIN1, and the inflammatory IL6 gene. *p < 0.05 and **p < 0.01 compared with differentiated control (Diff) metabolic and developmental processes including amino acid, fatty acid and neurotransmitter metabolism [20, 21]. Furthermore, PLP attenuates the production of oxygen reactive species [22] and the formation of advanced glycation end-products [23]. "
    [Show abstract] [Hide abstract] ABSTRACT: Aims/hypothesis We aimed to investigate the potential mechanisms involved in the compromised adipogenesis of visceral (VAT) vs subcutaneous adipose tissue (SAT) using comparative metabolomics. Based on the differentially identified metabolites, we focused on the relationship between the active form of vitamin B6 (pyridoxal 5-phosphate [PLP]), known to be generated through pyridoxal kinase (PDXK), and adipogenesis. Methods Non-targeted metabolomics analyses were performed in paired VAT and SAT (n = 14, discovery cohort). PDXK gene expression was evaluated in two validation cohorts of paired SAT and VAT samples in relation to obesity status and insulin sensitivity, and mechanistically after weight loss in vivo and in 3T3-L1 cells in vitro. Results Comparative metabolomics showed that PLP was significantly decreased in VAT vs SAT. Concordantly, PDXK mRNA levels were significantly decreased in VAT vs SAT, specifically in adipocytes. The decrease was specially marked in obese individuals. PDXK mRNA levels showed a strong association with adipogenic, lipid-droplet-related and lipogenic genes. At a functional level, systemic insulin sensitivity positively associated with PDXK expression, and surgically-induced weight loss (improving insulin sensitivity) led to increased SAT PDXK mRNA levels in parallel with adipogenic genes. In human pre-adipocytes, PDXK mRNA levels increased during adipocyte differentiation and after administration of peroxisome proliferator-activated receptor-γ agonists, and decreased under inflammatory stimuli. Mechanistic studies in 3T3-L1 cells showed that PLP administration resulted in increased adipogenic mRNA markers during early adipogenesis, whereas the PLP antagonist 4-deoxypyridoxine exerted opposite effects. Conclusions/interpretation Overall, these results support the notion that in situ production of PLP is required for physiological adipogenesis.
    Full-text · Article · Feb 2016
    • "As stated above, vitamin B 6 in its form as PLP is required as a cofactor for both auxin and ethylene biosynthesis (Mooney and Hellmann, 2010; Fitzpatrick, 2011). Therefore, the lower abundance and impaired ability to produce these hormones, respectively, in pdx1.3 in particular, may be simply linked to a stronger deficiency in the vitamin related to the fact that PDX1.3 is more abundant than PDX1.1 (Titiz et al., 2006). "
    [Show abstract] [Hide abstract] ABSTRACT: Vitamin B6 (pyridoxal 5'-phosphate) is an essential cofactor of many metabolic enzymes. Plants biosynthesize the vitamin de novo employing two enzymes, PDX1 and PDX2. In Arabidopsis, there are two catalytically active paralogs of PDX1 (PDX1.1, PDX1.3) producing the vitamin at comparable rates. Since single mutants are viable but the pdx1.1 pdx1.3 double mutant is lethal, the corresponding enzymes seem redundant. However, the single mutants exhibit substantial phenotypic differences, particularly at the level of root development, with pdx1.3 being more impaired than pdx1.1. Here we investigate the differential regulation of PDX1.1 and PDX1.3 by identifying factors involved in their disparate phenotypes. Swapped promoter experiments clarify the presence of distinct regulatory elements in the upstream regions of both genes. Exogenous sucrose triggers impaired ethylene production in both mutants but is more severe in pdx1.3 than pdx1.1. Interestingly, sucrose specifically represses PDX1.1 expression, accounting for the stronger vitamin B6 deficit in pdx1.3 compared to pdx1.1. Surprisingly, sucrose enhances auxin levels in pdx1.1, whereas the levels are diminished in pdx1.3. In the case of pdx1.3, the previously reported reduced meristem activity combined with the impaired ethylene and auxin levels manifests the specific root developmental defects. Moreover, it is the deficit in ethylene production and/or signaling that triggers this outcome. On the other hand, we hypothesize that it is the increased auxin content of pdx1.1 that is responsible for root developmental defects observed therein. We conclude that PDX1.1 and PDX1.3 play partially non-redundant roles and are differentially regulated as manifested in disparate root growth impairment morphologies. Copyright © 2014, American Society of Plant Biologists.
    Full-text · Article · Jan 2015
    • "Due to its involvement in various cellular metabolic processes , VB 6 availability is expected to augment the process of carcinogenesis by keeping the DNA synthesis machinery functional through SHMT1 catalyzed reactions [20]. Consequently, VB 6 uptake from the neighboring tissues increases to support tumor growth [4,21]. In short, the increased DNA requirement enhances SHMT1 activity [6,22] which enforces increased VB 6 uptake in cancer cells than normal cells [6,17,20] and therefore a vector coupled to VB 6 may experience enhanced cellular uptake [17,23,24]. "
    [Show abstract] [Hide abstract] ABSTRACT: Serine hydroxymethyltransferase isoforms (SHMT1 & SHMT2α), which serve as scaffold protein for the formation of a multi-enzyme complex and generate one-carbon unit for the de novo thymidylate biosynthesis pathway during DNA synthesis, are vitamin B6 (VB6)-dependent enzyme. Cancer cells with high proliferation intensity need increased SHMT activation which enforces the facilitated-diffusion of VB6 for the continuous functioning of thymidylate synthase cycle. Therefore, SHMT knockdown presents an alternative approach to prevent DNA synthesis in cancer cells; however, its potential to inhibit cancer growth remains unknown so far. Here we demonstrated that VB6 coupled to poly(ester amine) (VBPEA) enforces a high level of VTC (VB6-transporting membrane carriers)-mediated endocytosis of the complexed SHMT1 siRNA (siSHMT1) to interrupt the thymidylate biosynthesis pathway of cancer cells. The detrimental effect of SHMT1 knockdown on the disintegration of multi-enzyme complex resulted in cell cycle arrest and a decrease in cell's genomic DNA content, leading to enhanced apoptotic events in cancer cells. A reduction in tumor size was observed with constant SHMT1 suppression in xenograft mice. This study illustrates how silencing the SHMT1 expression inhibits cancer growth and the increased VB6 channeling for sustenance of cancer cells promotes VB6-coupled vector to elicit enhanced delivery of siSHMT1.
    Full-text · Article · Aug 2014
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